Polymeric compositions comprising at least one volume excluding polymer

ABSTRACT

The present invention relates to compositions comprising a polymeric substrate comprising at least one volume excluding polymer. In one embodiment, the present invention provides polymeric articles that are capable of acting as osmotic drivers. The articles are capable of maintaining a desired water balance by moving water in or out of a substrate to maintain cation concentration equilibrium between the substrate and its environment.

RELATED APPLICATIONS

This application claims priority from U.S. provisional application Ser.No. 60/863,755, which is incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

It is known that contact lenses can be used to improve vision, andvarious contact lenses have been commercially produced for many years.Hydrogel contact lenses are very popular today. These lenses are oftenmore comfortable to wear than contact lenses made of hard materials.

One popular contact lens material used for daily and weekly wear isEtafilcon, based on 2-hydroxyethyl methacrylate (HEMA) and a smallamount of methacrylic acid. The acidic moiety increases thehydrophilicity of the HEMA material, making a more comfortable lens.

Contact lenses made from silicone hydrogels have been disclosed.Silicone hydrogel contact lenses allow greater amounts of oxygen thanconventional lenses (such as HEMA based lenses) through the lens to theeye. However, the silicone materials are not inherently wettable, andcoatings and wetting agents have been used to improve the wettability ofthe lens. Mucin balls are known to develop in the wearer of somesilicone hydrogel contact lenses, caused by the shearing force betweenthe eyelid and the material. The long-term effects of this have yet tobe discovered.

SUMMARY OF THE INVENTION

The present invention relates to a composition comprising a polymercomprising at least one volume excluding polymer.

The present invention further relates to a device formed from a hydratedpolymer and at least one volume excluding polymer in a concentrationsufficient to act as an osmotic driver.

The present invention further relates to a method comprisingincorporating at least one volume excluding polymer in or on at leastone substrate.

DESCRIPTION OF THE FIGURES

FIG. 1 is a diagram of the dynamic vapor sorption analyzer used in theExamples.

FIG. 2 is a graph of the relative mass loss of control lenses and lensesof the present invention as a function of time.

FIG. 3 is a graph of the relative mass loss of three commerciallyavailable lenses and a sample of healthy human cornea as a function oftime.

DESCRIPTION OF THE INVENTION

As used herein, volume excluding polymer are polymers comprisinghydratable polyanions which by virtue of charge repulsion in the chargedstate and the size of the anionic groups have the ability to excludeother groups from the surface on which they are incorporated. In oneembodiment, the hydratable polyanions will possess an excluding volumegreater than that possessed by carboxylate groups at physiological pH,such as those between about 5 to about 8. Suitable anionic groupsinclude phosphates, phosphonates, borates, sulfates, sulfonates,combinations thereof and the like. In one embodiment the anionic groupcomprises at least one sulfonate group. In another embodiment, theanionic group is sulfonate.

The volume excluding polymers may be formed from reactive anionicmonomers which comprise the hydratable polyanion groups and at least onereactive group, which permits incorporation of the reactive anionicmonomer into the volume excluding polymer.

Examples of suitable reactive anionic monomers include

R-L-A

Wherein R is a reactive group, L is a linking group and A is an anionicgroup as defined above.

Reactive groups, R, include groups that that can undergo free radicaland/or cationic polymerization, condensation polymerization, ringopening polymerization and the like. Non-limiting examples of freeradical reactive groups include (meth)acrylates, styryls, vinyls, vinylethers, C₁₋₆alkyl(meth)acrylates, (meth)acrylamides,C₁₋₆alkyl(meth)acrylamides, N-vinyllactams, N-vinylamides,C₂₋₁₂alkenyls, C₂₋₁₂alkenylphenyls, C₂₋₁₂alkenylnaphthyls,C₂₋₆alkenylphenylC₁₋₆alkyls, O-vinylcarbamates and O-vinylcarbonates.Non-limiting examples of cationic reactive groups include vinyl ethersor epoxide groups and mixtures thereof. In one embodiment the reactivegroup comprises (meth)acrylate, acryloxy, (meth)acrylamide, and mixturesthereof. As used herein “(meth)acrylate” includes both acrylate andmethacrylate.

Non-limiting examples groups capable of undergoing condensationpolymerization include alcohols, esters, carboxylic acids, isocyanates,anhydrides, groups capable of halide displacement, such as phenylchloride, combinations thereof and the like.

Non limiting examples of groups capable of undergoing ring openingpolymerization include cyclic derivatives of hydroxyl and aminocarboxycylic acids, cyclic ethers, cyclic esters, cyclic amides,combinations thereof and the like.

Non limiting examples of groups capable of undergoing ring openingpolymerization include cyclic ethers, cyclic esters, cyclic amides,combinations thereof and the like.

L is a divalent linking group comprising substituted and unsubstitutedalkylene having 1-12 carbon atoms, which may be straight or branched,polyethers, oxazolines, substituted and unsubstituted heterocyclicgroups. Suitable substituents include aryl, amine, ether, amide,hydroxyl groups, combinations thereof and the like. In anotherembodiment, L comprises straight or branched alkylene group having 2 to8 carbons. In one embodiment the reactive anions of the presentinvention have the formula

H₂C═C(R₂)—CO₂—(CH₂)_(n)-A

Wherein R₂ is selected from —H, —CH₃, —CH₂CO₂—(CH₂)_(n)-A, where n is aninteger between 2 and 8 and A is as defined above. In one embodiment nis 2 to 6.

The reactive anionic monomers are polymerized, either alone or withcomonomers to form the volume excluding polymer. Suitable volumeexcluding polymers may have a wide range of molecular weights, so longas the desired concentration of hydratable polyanions is present at thesubstrate surface. This may be accomplished by grafting oligomers of 3or more repeat units onto the substrate or by incorporating polymerhaving a molecular weight within a wide range. Accordingly, the volumeexcluding polymer may be an oligomer having a molecular weight of atleast about 500, or may be a polymer having a molecular weight of atleast about 1000, and in some embodiments, between about 1000 andseveral million, as measured via any of the well known methods in theart such as GPC, viscosity and the like. Mixtures of volume excludingpolymers having different molecular weights may also be used. Forexample, in some embodiments it may be desirable to use a mixture ofvolume excluding polymers, with each of the polymers having differentmolecular weights. In one non-limiting embodiment, where it is desiredto have anionic groups close to the substrate surface and also spacedfrom the substrate surface at least two distinct volume excludingpolymers, one having a relatively low molecular weight of less thanabout 10,000 and a second volume excluding polymer with a high molecularweight of greater than 100,000 might be used. Other combinations will beapparent to those of skill in the art using the teachings of the presentinvention.

The volume excluding polymers suitable for use in the present inventionare hydrolytically stable, and in some embodiments thermally stable aswell.

Generally a physiologically compatible cation is ionically associated tothe anionic groups. When the substrate of the present invention is anophthalmic devices such as a contact lens, suitable cations include Li+,Na⁺, K⁺, NH₄ ⁺, Mg⁺, Zn⁺, Ag+, combinations thereof and the like. Insome embodiments, the cations comprise Na⁺, K⁺, NH₄ ⁺ and mixturesthereof. Additional cations may also be present as salts in thesolutions which are used with the ophthalmic devices of the presentinvention, including but not limited to Ca⁺, Mg⁺, Zn⁺, Ag⁺ and the like.

Examples of suitable reactive anionic monomers include, but are notlimited to of sodium-2-(acrylamido)-2-methylpropane sulphonate,3-sulphopropyl (meth)acrylate potassium salt, 3-sulphopropyl(meth)acrylate sodium salt, bis 3-sulphopropyl itaconate di sodium, bis3-sulphopropyl itaconate di potassium, vinyl sulphonate sodium salt,vinyl sulphonate salt, styrene sulfonate and mixtures thereof.

In some embodiments the volume excluding polymer may also formed fromreactive anionic monomers where L comprises amine functionality. Theseamine functional reactive anionic monomers have a balanced charge, andmay be desirable for substrates where low swelling is desired. However,to achieve the desired osmotic effect, at least about 20 wt % of thevolume excluding polymer should comprise repeating units derived fromthe reactive anionic monomers.

The volume excluding polymers comprise between about 20 and about 80 wt% repeating units derived from reactive anionic monomer(s) and in someembodiments between about 40 and about 75 wt %.

The volume excluding polymers may also include comonomers. Thecomonomers may be distributed throughout the volume excluding polymer inany way, including randomly distributed, distributed in blocks or acombination thereof. In one embodiment, when comonomers are present,they are distributed through the polymer so that they do not providesubstantial gaps in the volume excluded by the anionic groups. Inembodiments where the volume excluding polymer is associated with thelens via affinity interactions, the volume excluding polymer may includeblocks of comonomers with properties similar to those of the lenspolymer. For example, for a contact lens comprising silicone, thecomonomer may be a hydrophobic block, such as a hexylene, or may be apendant hydrophobic group, such as a pendant siloxane group.

In one embodiment, the comonomers may be selected from monofunctionalhydrophilic monomers, such as, but not limited to acrylic- orvinyl-containing monomers. The term “vinyl-type” or “vinyl-containing”monomers refer to monomers containing the vinyl grouping (—CH═CH₂) andare generally highly reactive. Such hydrophilic vinyl-containingmonomers are known to polymerize relatively easily.

“Acrylic-type” or “acrylic-containing” monomers are those monomerscontaining the acrylic group: (CH₂═CRCOX) wherein R is H or CH₃, and Xis O or N, which are also known to polymerize readily, such asN,N-dimethyl acrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA),glycerol methacrylate, 2-hydroxyethyl methacrylamide, hydroxyethylacrylamide, polyethyleneglycol mono(meth)acrylate, methacrylic acid andacrylic acid.

Hydrophilic vinyl-containing monomers which may used as the comonomersinclude N-vinyl amides, N-vinyl lactams (e.g. N-vinylpyrrolidone orNVP), N-vinyl acetamide, N-vinyl-N-methyl acetamide, N-vinyl-N-ethylacetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide, 2,2-di methoxy,1-hydroxy acrylamide, hydroxymethyl diacetone acrylamide, N-acryloylmorpholine, hydroxyl methylacrylamide, combinations thereof and thelike.

Other hydrophilic monomers that can be employed in the invention includepolyoxyethylene polyols having one or more of the terminal hydroxylgroups replaced with a functional group containing a polymerizabledouble bond. Examples include polyethylene glycol, ethoxylated alkylglucoside, and ethoxylated bisphenol A reacted with one or more molarequivalents of an end-capping group such as isocyanatoethyl methacrylate(“IEM”), toluoylmeta isocyanate (TMI), methacrylic anhydride,methacryloyl chloride, vinylbenzoyl chloride, or the like, to produce apolyethylene polyol having one or more terminal polymerizable olefinicgroups bonded to the polyethylene polyol through linking moieties suchas carbamate or ester groups.

Still further examples are the hydrophilic vinyl carbonate or vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215, and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277.Other suitable hydrophilic monomers will be apparent to one skilled inthe art.

In one embodiment the comonomer comprises at least one hydrophilicmonomer selected from DMA, HEMA, glycerol methacrylate, 2-hydroxyethylmethacrylamide, NVP, N-vinyl-N-methyl acrylamide,N-methyl-N-vinylacetamide, polyethyleneglycol monomethacrylate,methacrylic acid, acrylic acid, N-(tris(hydroxymethyl)methyl)acrylamide,itaconic acid and combinations thereof.

In another embodiment, the volume excluding polymer comprises comonomerscontaining at least one amide group, carboxyl, hydroxyl group, ormixtures thereof. Comonomers of these types may have the R-L groupsdefined above, and further comprise at least one amide, carboxylic acidor hydroxyl in place of the polyanionic group or may have the amide,carboxylic acid or hydroxyl group bonded directly to R, as definedabove. Suitable amide groups have the structure

where R₃ and R₄ are independently selected from H, straight or branchedC₁₋₁₂ alkyls which may be ether substituted.

In one embodiment the volume excluding polymer is formed from thefollowing monomers in the following amounts:

Mol. %, based upon all reactive components Embodi- Embodi- Embodi-monomer ment 1 ment 2 ment 3 Reactive anionic monomer  2-100 30-60 40-55Amide containing comonomer 2-80 15-45 25-45 Carboxylic acid containing0-40 10-30 15-25 comonomer Hydroxyl containing 0-40 10-30 15-25comonomer

The volume excluding polymer may also comprise at least one hydrophobiccomonomer in addition or instead of the above listed hydrophilicmonomers. Any of the silicone monomers described below may be used aswell as any other hydrophobic monomers which are known to be useful forthe manufacture of biomedical devices, such as rigid or hard contactlenses or IOLs.

In some embodiments it is desirable for the volume excluding polymer tohave a structure with the hydratable polyanion groups extending out fromthe polymer backbone. In another embodiment the hydratable polyaniongroups extend out from the polymer backbone and are freely rotatable.Examples of suitable structures include a brush structure, a branchedstructure a loop structure and combinations thereof. In a brushstructure the hydratable polyanion groups extend pendantly along thepolymer backbone for form a comb or brush structure. In a branchedstructure, the hydratable polyanions extend pendantly from thenon-reaction terminal end of the volume excluding polymer. In a loopstructure the hydratable polyanion groups are bound to the backbone ofthe volume excluding polymer in at least two places forming a loop orbridge with the polymer backbone.

The volume excluding polymer may be used on with biomedical devices. Asused herein biomedical devices include those designed to be used whilein or on either or both mammalian tissue or fluid and in one embodimenthuman tissue or fluid. Examples of such devices include, withoutlimitation, stents, implants, catheters, wound dressings, intervertebraldisk replacements, sensor devices, diagnostic equipment and ophthalmicdevices, including punctal plugs, ophthalmic lenses and ophthalmicinserts. In one embodiment, the biomedical device is an ophthalmic lensincluding, without limitation, contact or intraocular lenses. In anotherembodiment the device is a soft contact lens, and in some cases asilicone hydrogel contact lens.

The medical devices may be made from any material known to be usefultherefor. In one embodiment the medical device is made from at lest onepolymer. For simplicity the methods for attachment will be describedwith reference to one embodiment where the medical device is a contactlens. Those of skill in the art, using the teaching of the presentinvention will be able to apply the present invention to other medicaldevices.

The volume excluding polymer may be covalently or ionically attached toat least a portion of at least one surface of the substrate, may beincorporated into a coating composition which applied to the surface ofthe substrate, may be imbibed into all or part of the substrate or maybe polymerized with the reactive mixture from which the substrate ismade, or a combination of the above methods.

In embodiments where the volume excluding polymer is covalentlyattached, both the substrate polymer and the volume excluding polymerwill have reactive groups capable of reacting to form a covalent bond.Any method capable of forming a covalent bond which will remain stableduring the use of the substrate may be used. According, free radicalreactions, condensation and esterification reactions, ring openingreactions, and the like. If the substrate polymer does not have theappropriate reactive groups it can be pretreated to generate the desiredgroups. In one embodiment, the volume excluding polymer comprising afree radical reactive compound, and is contacted with at least onesurface of the substrate in coating effective amounts and under coatingeffective conditions to coat the desired substrate surface.

The volume excluding polymer may be incorporated in to a solution tofacilitate the coating process. For example, the volume excludingpolymer and any other desired components such as initiators,crosslinkers, colorants, photochromic compounds, stabilizers, chaintransfer agents, humectants, wetting agents, antimicrobial compounds,therapeutic compounds, combinations thereof and the like may be combinedin a solvent. In some embodiments, it may be desirable for certain ofthe additional compounds, such as, but not limited to humectants,wetting agents, antimicrobial compounds, therapeutic compounds andmixtures thereof to elute from the article. Suitable solvents willdissolve the volume excluding polymer and other coating compositioncomponents, but will not dissolve or substantially swell the biomedicaldevice. For example, when the biomedical device is a contact lens,suitable examples of solvents include water, acetonitrile, watermiscible alcohols, polyethers, combinations thereof and the like.Specific examples include alkoxy alcohols, alkoxy polyols, glycerolborate esters, combinations thereof and the like. Specific examplesinclude tripropylene glycol, ethoxy ethanol, methoxy ethanol,dipropylene glycol, propylene glycol, alkoxy trimethylene glycol,N-propanol, isopropanol, t-amyl alcohol, t-butanol, monoethyl ether,combinations thereof and the like.

The volume excluding polymer is incorporated in the solvent in a coatingeffective amount. As used herein a coating effective amount is an amountsufficient to provide a coherent coating on the article surface. Thecoating effective amount will vary depending on the type of coatingprocess selected. For example, for solution grafting amounts from about5 weight %, and in some embodiments between about 5 and about 10 weight% based upon all components in the coating solution. Those of skill inthe art will be able to determine suitable ranges for other coatingprocessing using the teachings of this invention.

The biomedical device is contact with the solution via any convenientmeans. Suitable contacting means include spraying, dipping, wiping,rolling, combinations thereof and the like. The entire device may becoated, one surface of a device may be coated or only a portion of asurface may be coated. For example, when the biomedical device is acontact lens, the entire lens may be coated, only one side of the lensmay be coated (for example either the back curve which rests on thecornea and conjuctiva, or the front surface which is in contact with theeyelids and air), or only a portion of a surface may be coated (forexample a portion of either surface which covers the iris, pupil orconjuctiva).

The device is contacted with the solvent/coating polymer solution underconditions suitable to form the coating. Suitable temperatures includethose between the freezing and boiling points of the selected solvent,preferably between about 0 and about 100° C. and more preferably betweenabout 15 and about 50° C. The contact time used will be a length of timesufficient to coat the surface to the extent desired. Contact times maybe up to about 2 days, in some embodiments up to about 1 day, and insome embodiments up to about 12 hours, and in another embodiment up toabout 1 hour. Pressure is not critical in the coating reaction of thepresent invention. However, those of skill in the art will recognizethat elevated pressures and temperatures may enable the reaction to beconducted in a shorter period of time. It should be appreciated that theconcentration of the hydratable polyanion in the graft solution,reaction temperature and time are all related, and that higherconcentrations of hydratable polyanion and/or increased temperatures mayallow for shorter reaction times.

Alternatively, the reactive polyanion groups may be contacted with thesubstrate under polymerization effective conditions, and polymerized inthe presence of the substrate. Suitable polymerization conditions willdepend on the reactive polyanion groups selected. For example, forsubstrates containing hydroxyl groups at or near the surface freeradical reactive hydratable polyanions, such as the potassium salt of3-sulfopropylester acrylate (SPA), may be graft polymerized using acatalyst which can abstract hydrogen atoms from adjacent hydroxyl groupssuch as ammonium cerium (IV) nitrate (CAN). However, any known graftingtechniques which creates reactive sites on the desired substrate may beused. The SPA and catalyst are mixed is a solvent which swells theselected substrate to form a graft solution. The concentration ofreactive polyanion groups may vary from about 5 to about 100 weight %,and in some embodiments from about 50 to about 100 weight % in thecoating solution. The catalyst is present in amounts between about 0.01and about 1 weight % and in some embodiments between about 0.05 andabout 0.1 weight % based upon the weight of the catalyst and volumeexcluding polymer components (reactive anionic monomers and comonomers).

Crosslinkers may be included in the coating solutions of the presentapplication. The amount of crosslinker included will vary depending uponthe article substrate selected. For examples, where the substrate isformed from a polymer having an anionic charge, the selected catalystmay penetrate the substrate polymer network and no crosslinker, or verylittle crosslinker may need to be used. In other embodiments, where thesubstrate is formed from a polymer having a neutral charge, it may bedesirable to include at least one crosslinker in the coating solution inan amount sufficient to provide the desired level of coating integrityand permanence of coating between the volume excluding polymer and thesubstrate for the intended end use. For example, in an embodiment wherethe substrate is a contact lens, the coating should remain throughoutthe wear schedule, and should have the integrity necessary to providethe desired benefit across the relevant portion of the lens surface.When a crosslinker is used, Suitable crosslinker concentrations includefrom 0 to about 3 weight % and in some embodiments from about 0 to about1%. Suitable crosslinkers include, but are not limited to dicappedpolyethylene glycols, more specific examples include methylenebisacrylamide, ethylene glycol dimethacrylate, polyethylgycoldimethacrylate, tetraethylene GDMA, diallyl tartramide, pentaerithratoldiacrylate, divinyl benzene combinations thereof and the like.

For water swellable substrates, such as soft contact lenses, the watercontent of the substrate may also affect efficiency of the graftreaction. Accordingly it may be desirable to adjust the level ofgrafting to achieve desired effect, or to coat the substrate with volumeexcluding polymer having a molecular weight which is sufficiently highto prevent it from substantially intercalating into the substratepolymer network.

The grafting process may optionally include a pre-reactive step toprovide the substrate with properties which will enhance the efficiencyof grafting. For example, the substrate may be treated to increase theconcentration of reactive groups. Suitable preactivation steps are knownin the art and include oxidation process which produces reactive sites,including but not limited to plasma oxidation, reaction with potassiumpersulfate, reaction with iodate, combinations thereof and the like.

Alternatively, R may be any group capable of being activated by acoupling agent, or any group capable of reacting with a substratesurface which has been activated by a coupling agent. For example, adirect reaction may be accomplished by the use of a reagent or reactionthat activates a group in the surface polymer or volume the syntheticantimicrobial peptide making it reactive with a functional group on thepeptide or polymer, respectively, without the incorporation of acoupling agent. For example, one or more amine or alcohol or thiolgroups on the synthetic antimicrobial peptide may be reacted directlywith isothiocyanate, acyl azide, N-hydroxysuccinimide ester,pentafluorophenoxy ester, sulfonyl chloride, an aldehyde, glyoxalepoxide, carbonate, aryl halide, imido ester, tosylate ester or ananhydride group on the polymer.

In an alternative embodiment, coupling agents may be used. Couplingagents useful for coupling the cationic peptide or protein to thedevice's surface include, without limitation, N,N′-carbonyldiimidazole,carbodiimides such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide(“EDC”), dicyclohexyl carbodiimide,1-cylcohexyl-3-(2-morpholinoethyl)carbodiimide, diisopropylcarbodiimide, or mixtures thereof. The carbodiimides also may be usedwith N-hydroxysuccinimide or N-hydroxysulfosuccinimide to form estersthat can react with amines to form amides.

Amino groups also may be coupled to the polymer by the formation ofSchiff bases that can be reduced with agents such as sodiumcyanoborohydride and the like to form hydrolytically stable amine links.Coupling agents useful for this purpose include, without limitation,N-hydroxysuccinimide esters, such as dithiobis(succinimidylpropionate),3,3′-dithiobis(sulfosuccinimidylpropionate), disuccinimidyl suberate,bis(sulfosuccinimidyl) suberate, disuccinimidyl tartarate and the like,imidoesters, including, without limitation, dimethyl adipimate,difluorobenzene derivatives, including without limitation1,5-difluoro-2,4-dinitrobenzene, bromofunctional aldehydes, includingwithout limitation gluteraldehyde, and bis epoxides, including withoutlimitation 1,4-butanediol diglycidyl ether. One ordinarily skilled inthe art will recognize that any number of other coupling agents may beused depending on the functional groups present on the device's surface.

If the device's surface does not contain suitable reactive groups, suchsuitable groups may be incorporated into the polymer by any conventionalorganic synthesis methods. Alternatively, the reactive groups may beintroduced by the addition of polymerizable monomers containing reactivegroups into the monomer mixture used to form the polymer. As are knownby those in the art, any monomer with a labile hydrogen, such but notlimited to hydroxyl group, acid, acid chloride groups, carbodiimides,amines and the like, may be used. Reactive gas plasma processes may alsobe used.

Alternatively, the volume excluding polymer may be associated withpolymer substrate. The volume excluding polymer may be associated viaionic interactions, steric interactions, affinity interactions,adsorbtion, dispersive interactions, anionic charges, interpenetration,combinations thereof and the like. In this embodiment, the comonomers inthe volume excluding polymer are selected to provide the desiredinteraction. In this process the polymer substrate is contacted with asolution comprising the volume excluding polymer under conditions whichallow incorporation of the volume excluding polymer in the desiredamount. Methods such as those disclosed in U.S. Pat. Nos. 6,689,480,6,827,966, 6,451,871, 7,022,379, 6,858,248, WO 2004,060431 and EP1,287,060, the disclosures of which, and all other patents andapplications listed herein, is incorporated herein by reference.

In another embodiment the volume excluding polymer may be incorporatedvia a mold transfer process. Generally the mold transfer process wouldbe used to incorporate the volume excluding polymer as follows: coatinga molding surface of a mold or a mold half with a coating effectiveamount of a coating composition comprising at least one volume excludingpolymer; b.) dispensing the reaction mixture comprising thepolymerizable components selected to make the desired substrate into themold or mold half, and c.) curing under conditions suitable to form thedesired substrated coated with the coating composition. In someembodiments it may be desired to select the coating composition suchthat it will swell in the substrate reaction mixture. Further detailsrelating to mold transfer coating may be found in US-2003-0052424.

Other coating methods will be apparent to those of skill in the art, andare within the scope of the present invention.

In one embodiment, the volume excluding polymer is incorporated on atleast one surface of the substrate in an amount effective to prevent orresist dehydration of that surface of the substrate. For example, in oneembodiment where the substrate is a contact lens, the front surface ofthe contact lens, which is in contact with the eyelids during blinking,comprises a layer of at least one anionic volume excluding polymer. Thepolyanions in the volume excluding polymer associate with cations fromthe tear film. As the water on the front surface of the contact lensevaporates, the concentration of cations in the tear film on the lenssurface increases above the concentration of cations in the tears. Thiscreates an osmotic imbalance, which draws water from the tear film torestore the equilibrium concentration of cations to the water on thefront lens surface. Thus, in one embodiment, the volume excludingpolymers of the present invention act as osmotic drivers. As usedherein, osmotic drivers are components that move water in or out of asubstrate to maintain cation concentration equilibrium between thesubstrate and its environment.

The amount of water drawn from the tear film to the front surface of thelens may be controlled by the thickness of the coating of volumeexcluding polymer. In embodiments where the device is an ophthalmicdevice adapted to rest between the cornea or conjunctiva and any part ofthe eyelids, the volume excluding polymer is located primarily on theouter 5 um of the lens surface. Lenses with thicker layers or may have atendency to pull undesirable amounts of water from the tear fluid. Thus,another embodiment of the present invention includes devices which actas osmotic drivers, maintaining a desired water balance on or in thedevice. Other end uses for such osmotic drivers include, but are notlimited to wound healing materials, including dressings, and therapeuticophthalmic dressings, intervertebral disk replacements and the like.

Examples of polymers which may be used to form substrates suitable forthe present invention include, without limitation, polymers andcopolymers of styrene and substituted styrenes, ethylene, propylene,acrylates and methacrylates, N-vinyl lactams, acrylamides andmethacrylamides, acrylonitrile, acrylic and methacrylic acids as well aspolyurethanes, polyesters, polydimethylsiloxanes and mixtures thereof.Such polymers may include hydrogels and silicone hydrogels.

In one embodiment where the biomedical device is a contact lens,suitable polymers include polymers used to make soft contact lenses, andthose used to make hard contact lenses. Non-limiting examples ofsuitable soft contact lens formulations of include polymers andcopolymers of poly(meth)acrylates, including but not limited to silicone(meth)acrylates; poly(meth)acrylamides, polyvinylcarbonates,polyvinylcarbamates, polyvinylamides, polyvinyllactams, polyurethanes,polyvinyl alcohols and combinations thereof, and those formulationsdescribed in U.S. Pat. No. 5,710,302, WO 9421698, EP 406161, U.S. Pat.No. 5,998,498, U.S. Pat. No. 6,087,415, U.S. Pat. No. 5,760,100, U.S.Pat. No. 5,776,999, U.S. Pat. No. 5,789,461, U.S. Pat. No. 5,849,811,and U.S. Pat. No. 5,965,631. Non-limiting examples of soft contactlenses formulations include but are not limited to the formulations ofacquafilcon A, balafilcon A, galyfilcon A, senofilcon A, comfilcon andlotrafilcon A and B. Additional examples of suitable silicone hydrogelsinclude those disclosed in U.S. Pat. No. 5,998,498, WO03/22321, U.S.Pat. No. 6,087,415, U.S. Pat. No. 5,760,100, U.S. Pat. No. 5,776,999,U.S. Pat. No. 5,789,461, U.S. Pat. No. 5,849,811, U.S. Pat. No.5,965,631, U.S. Pat. No. 6,867,245, U.S. Pat. No. 6,822,016, U.S. Pat.No. 6,849,671, U.S. Pat. No. 7,052,131. These patents as well as allother patent disclosed in this paragraph are hereby incorporated byreference in their entirety. Where the medical device is a soft contactlens, the polymer will preferably be a hydrogel, and in some embodimentswill have water contents of at least about 5% and in some embodiments atleast about 20%.

Hard contact lenses are made from polymers that include but are notlimited to polymers and copolymers of poly(methyl)methacrylate, silicone(meth)acrylates, fluoro(meth)acrylates, fluoroethers, polyacetylenes,and polyimides, where the preparation of representative examples may befound in JP 200010055, JP 6123860 and U.S. Pat. No. 4,330,383.Intraocular lenses of the invention can be formed using known materials.For example, the lenses may be made from a rigid material including,without limitation, polymethyl methacrylate, polystyrene, polycarbonate,or the like, and combinations thereof. Additionally, flexible materialsmay be used including, without limitation, hydrogels, siliconematerials, acrylic materials, fluorocarbon materials and the like, orcombinations thereof. Typical intraocular lenses are described in WO0026698, WO 0022460, WO 9929750, WO 9927978, WO 0022459. U.S. Pat. Nos.4,301,012; 4,872,876; 4,863,464; 4,725,277; 4,731,079. All of thereferences mentioned in this application are hereby incorporated byreference in their entirety.

In one embodiment the substrate is formed from a reactive mixturecomprising at least one silicone containing component.

The term component includes monomers, macromers and prepolymers.“Monomer” refers to lower molecular weight compounds that can bepolymerized to higher molecular weight compounds, polymers, macromers,or prepolymers. The term “macromer” as used herein refers to a highmolecular weight polymerizable compound. Prepolymers are partiallypolymerized monomers or monomers which are capable of furtherpolymerization.

A “silicone-containing component” is one that contains at least one[—Si—O—] unit in a monomer, macromer or prepolymer. Preferably, thetotal Si and attached O are present in the silicone-containing componentin an amount greater than about 20 weight percent, and more preferablygreater than 30 weight percent of the total molecular weight of thesilicone-containing component. Useful silicone-containing componentspreferably comprise polymerizable functional groups such as acrylate,methacrylate, acrylamide, methacrylamide, vinyl, N-vinyl lactam,N-vinylamide, and styryl functional groups. Examples ofsilicone-containing components which are useful in this invention may befound in U.S. Pat. Nos. 3,808,178; 4,120,570; 4,136,250; 4,153,641;4,740,533; 5,034,461 and 5,070,215, and EP080539. These referencesdisclose many examples of olefinic silicone-containing components.

Suitable silicone containing components include compounds of Formula I

where

R¹ is independently selected from monovalent reactive groups, monovalentalkyl groups, or monovalent aryl groups, any of the foregoing which mayfurther comprise functionality selected from hydroxy, amino, oxa,carboxy, alkyl carboxy, alkoxy, amido, carbamate, carbonate, halogen orcombinations thereof; and monovalent siloxane chains comprising 1-100Si—O repeat units which may further comprise functionality selected fromalkyl, hydroxy, amino, oxa, carboxy, alkyl carboxy, alkoxy, amido,carbamate, halogen or combinations thereof;

where b=0 to 500, where it is understood that when bis other than 0, bisa distribution having a mode equal to a stated value;

-   -   wherein at least one R¹ comprises a monovalent reactive group,        and in some embodiments between one and 3 R¹ comprise monovalent        reactive groups.

As used herein “monovalent reactive groups” are groups that can undergofree radical and/or cationic polymerization. Non-limiting examples offree radical reactive groups include (meth)acrylates, styryls, vinyls,vinyl ethers, C₁₋₆alkyl(meth)acrylates, (meth)acrylamides,C₁₋₆alkyl(meth)acrylamides, N-vinyllactams, N-vinylamides,C₂₋₁₂alkenyls, C₂₋₁₂alkenylphenyls, C₂₋₁₂alkenylnaphthyls,C₂₋₆alkenylphenylC₁₋₆alkyls, O-vinylcarbamates and O-vinylcarbonates.Non-limiting examples of cationic reactive groups include vinyl ethersor epoxide groups and mixtures thereof. In one embodiment the freeradical reactive groups comprises (meth)acrylate, acryloxy,(meth)acrylamide, and mixtures thereof.

Suitable monovalent alkyl and aryl groups include unsubstitutedmonovalent C₁ to C₁₆alkyl groups, C₆-C₁₄ aryl groups, such assubstituted and unsubstituted methyl, ethyl, propyl, butyl,2-hydroxypropyl, propoxypropyl, polyethyleneoxypropyl, combinationsthereof and the like.

In one embodiment bis zero, one R¹ is a monovalent reactive group, andat least 3 R¹ are selected from monovalent alkyl groups having one to 16carbon atoms, and in another embodiment from monovalent alkyl groupshaving one to 6 carbon atoms. Non-limiting examples of siliconecomponents of this embodiment include2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propylester (“SiGMA”),2-hydroxy-3-methacryloxypropyloxypropyl-tris(trimethylsiloxy)silane,3-methacryloxypropyltris(trimethylsiloxy)silane (“TRIS”),3-methacryloxypropylbis(trimethylsiloxy)methylsilane and3-methacryloxypropylpentamethyl disiloxane.

In another embodiment, bis 2 to 20, 3 to 15 or in some embodiments 3 to10; at least one terminal R¹ comprises a monovalent reactive group andthe remaining R¹ are selected from monovalent alkyl groups having 1 to16 carbon atoms, and in another embodiment from monovalent alkyl groupshaving 1 to 6 carbon atoms. In yet another embodiment, bis 3 to 15, oneterminal R¹ comprises a monovalent reactive group, the other terminal R¹comprises a monovalent alkyl group having 1 to 6 carbon atoms and theremaining R¹ comprise monovalent alkyl group having 1 to 3 carbon atoms.Non-limiting examples of silicone components of this embodiment include(mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether terminatedpolydimethylsiloxane (400-1000 MW)) (“OH-mPDMS”), monomethacryloxypropylterminated mono-n-butyl terminated polydimethylsiloxanes (800-1000 MW),(“mPDMS”).

In another embodiment bis 5 to 400 or from 10 to 300, both terminal R¹comprise monovalent reactive groups and the remaining R¹ areindependently selected from monovalent alkyl groups having 1 to 18carbon atoms which may have ether linkages between carbon atoms and mayfurther comprise halogen.

In another embodiment, one to four R¹ comprises a vinyl carbonate orcarbamate of the formula:

wherein: Y denotes O—, S— or NH—;

R denotes, hydrogen or methyl; d is 1, 2, 3 or 4; and q is 0 or 1.

The silicone-containing vinyl carbonate or vinyl carbamate monomersspecifically include:1,3-bis[4-(vinyloxycarbonyloxy)but-1-yl]tetramethyl-disiloxane;3-(vinyloxycarbonylthio) propyl-[tris (trimethylsiloxy)silane];3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate;trimethylsilylethyl vinyl carbonate; trimethylsilylmethyl vinylcarbonate, and

Where biomedical devices with modulus below about 200 are desired, onlyone R¹ shall comprise a monovalent reactive group and no more than twoof the remaining R¹ groups will comprise monovalent siloxane groups.

In one embodiment, where a silicone hydrogel lens is desired, the lensof the present invention will be made from a reactive mixture comprisingat least about 20 and preferably between about 20 and 70% wt siliconecontaining components based on total weight of reactive monomercomponents from which the polymer is made.

Another class of silicone-containing components includes polyurethanemacromers of the following formulae:

Formulae IV-VI

(*D*A*D*G)_(α)*D*D*E¹;

E(*D*G*D*A)_(α)*D*G*D*E¹ or;

E(*D*A*D*G)_(α)*D*A*D*E¹

wherein:

D denotes an alkyl diradical, an alkyl cycloalkyl diradical, acycloalkyl diradical, an aryl diradical or an alkylaryl diradical having6 to 30 carbon atoms,

G denotes an alkyl diradical, a cycloalkyl diradical, an alkylcycloalkyl diradical, an aryl diradical or an alkylaryl diradical having1 to 40 carbon atoms and which may contain ether, thio or amine linkagesin the main chain;

* denotes a urethane or ureido linkage;

_(α) is at least 1;

A denotes a divalent polymeric radical of formula:

R¹¹ independently denotes an alkyl or fluoro-substituted alkyl grouphaving 1 to 10 carbon atoms which may contain ether linkages betweencarbon atoms; y is at least 1; and p provides a moiety weight of 400 to10,000; each of E and E¹ independently denotes a polymerizableunsaturated organic radical represented by formula:

wherein: R¹² is hydrogen or methyl; R¹³ is hydrogen, an alkyl radicalhaving 1 to 6 carbon atoms, or a —CO—Y—R¹⁵ radical wherein Y is —O—,Y—S— or —NH—; R¹⁴ is a divalent radical having 1 to 12 carbon atoms; Xdenotes —CO— or —OCO—; Z denotes —O— or —NH—; Ar denotes an aromaticradical having 6 to 30 carbon atoms; w is 0 to 6; x is 0 or 1; y is 0 or1; and z is 0 or 1.

A preferred silicone-containing component is a polyurethane macromerrepresented by the following formula:

wherein R¹⁶ is a diradical of a diisocyanate after removal of theisocyanate group, such as the diradical of isophorone diisocyanate.Another suitable silicone containing macromer is compound of formula X(in which x+y is a number in the range of 10 to 30) formed by thereaction of fluoroether, hydroxy-terminated polydimethylsiloxane,isophorone diisocyanate and isocyanatoethylmethacrylate.

Other silicone containing components suitable for use in this inventioninclude those described is WO 96/31792 such as macromers containingpolysiloxane, polyalkylene ether, diisocyanate, polyfluorinatedhydrocarbon, polyfluorinated ether and polysaccharide groups. U.S. Pat.Nos. 5,321,108; 5,387,662 and 5,539,016 describe polysiloxanes with apolar fluorinated graft or side group having a hydrogen atom attached toa terminal difluoro-substituted carbon atom. US 2002/0016383 describehydrophilic siloxanyl methacrylates containing ether and siloxanyllinkages and crosslinkable monomers containing polyether andpolysiloxanyl groups. Any of the foregoing polysiloxanes can also beused as the silicone containing component in this invention.

The reactive mixture may also comprise at least one hydrophiliccomponent. Hydrophilic monomers can be any of the hydrophilic monomersknown to be useful to make hydrogels.

One class of suitable hydrophilic monomers include acrylic- orvinyl-containing monomers. Such hydrophilic monomers may themselves beused as crosslinking agents, however, where hydrophilic monomers havingmore than one polymerizable functional group are used, theirconcentration should be limited as discussed above to provide a contactlens having the desired modulus. The term “vinyl-type” or“vinyl-containing” monomers refer to monomers containing the vinylgrouping (—CH═CH₂) and are generally highly reactive. Such hydrophilicvinyl-containing monomers are known to polymerize relatively easily.

“Acrylic-type” or “acrylic-containing” monomers are those monomerscontaining the acrylic group: (CH₂═CRCOX) wherein R is H or CH₃, and Xis O or N, which are also known to polymerize readily, such asN,N-dimethyl acrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA),glycerol methacrylate, 2-hydroxyethyl methacrylamide, polyethyleneglycolmonomethacrylate, methacrylic acid and acrylic acid.

Hydrophilic vinyl-containing monomers which may be incorporated into thesilicone hydrogels of the present invention include monomers such asN-vinyl amides, N-vinyl lactams (e.g. N-vinylpyrrolidone or NVP),N-vinyl-N-methyl acetamide, N-vinyl-N-ethyl acetamide, N-vinyl-N-ethylformamide, N-vinyl formamide, with NVP being preferred.

Other hydrophilic monomers that can be employed in the invention includepolyoxyethylene polyols having one or more of the terminal hydroxylgroups replaced with a functional group containing a polymerizabledouble bond. Examples include polyethylene glycol, ethoxylated alkylglucoside, and ethoxylated bisphenol A reacted with one or more molarequivalents of an end-capping group such as isocyanatoethyl methacrylate(“IEM”), methacrylic anhydride, methacryloyl chloride, vinylbenzoylchloride, or the like, to produce a polyethylene polyol having one ormore terminal polymerizable olefinic groups bonded to the polyethylenepolyol through linking moieties such as carbamate or ester groups.

Still further examples are the hydrophilic vinyl carbonate or vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215, and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277.Other suitable hydrophilic monomers will be apparent to one skilled inthe art.

In one embodiment the hydrophilic monomer comprises at least one of DMA,HEMA, glycerol methacrylate, 2-hydroxyethyl methacrylamide, NVP,N-vinyl-N-methyl acrylamide, N-methyl-N-vinylacetamide,polyethyleneglycol monomethacrylate, methacrylic acid and acrylic acid,In one embodiment the hydrophilic monomer comprises DMA.

The hydrophilic monomers may be present in a wide range of amounts,depending upon the specific balance of properties desired. Amounts ofhydrophilic monomer up to about 50 and preferably between about 5 andabout 50 weight %, based upon all components in the reactive componentsare acceptable. For example, in one embodiment lenses of the presentinvention comprise a water content of at least about 30%, and in anotherembodiment between about 30 and about 70%. For these embodiments, thehydrophilic monomer may be included in amounts between about 20 andabout 50 weight %.

Reactive and non-reactive wetting agents disclosed in US2003/0162862,US05/06640, US2006/0072069, WO2006/039276 may also be included. Whenwetting agents are used it may also be desirable to include acompatibilizing component. Suitable compatiblizing components includethose meeting the compatibility test disclosed in US2003/0162862. Any ofthe silicone components described above may be converted intocompatibilizing components by incorporating compatibilizing groups, suchas hydroxyl groups, in their structure. In some embodiments, the Si toOH ratio is less than about 15:1, and in others between about 1:1 toabout 10:1. Non-limiting examples of compatibilizing components include(mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether terminatedpolydimethylsiloxane (400-1000 MW)), “OH-mPDMS”,2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propylester “SiGMA”,2-hydroxy-3-methacryloxypropyloxypropyl-tris(trimethylsiloxy)silane,combinations thereof and the like.

Additional components such as, colorants, photochromic compounds,stabilizers, chain transfer agents, humectants, wetting agents,antimicrobial compounds, therapeutic compounds, combinations thereof andthe like may also be included in the reactive mixture. In someembodiments, it may be desirable for certain of the additionalcompounds, such as, but not limited to humectants, wetting agents,antimicrobial compounds, therapeutic compounds and mixtures thereof toelute from the article.

A polymerization catalyst may be included in the reaction mixture. Thepolymerization initiators includes compounds such as lauryl peroxide,benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, andthe like, that generate free radicals at moderately elevatedtemperatures, and photoinitiator systems such as aromatic alpha-hydroxyketones, alkoxyoxybenzoins, acetophenones, acylphosphine oxides,bisacylphosphine oxides, and a tertiary amine plus a diketone, mixturesthereof and the like. Illustrative examples of photoinitiators are1-hydroxycyclohexyl phenyl ketone,2-hydroxy-2-methyl-1-phenyl-propan-1-one,bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide(DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenyl phosphineoxide (Irgacure819), 2,4,6-trimethylbenzyldiphenyl phosphine oxide and2,4,6-trimethylbenzoyl diphenylphosphine oxide, benzoin methyl ester anda combination of camphorquinone and ethyl 4-(N,N-dimethylamino)benzoate.Commercially available visible light initiator systems include Irgacure819, Irgacure 1700, Irgacure 1800, Irgacure 819, Irgacure 1850 (all fromCiba Specialty Chemicals) and Lucirin TPO initiator (available fromBASF). Commercially available UV photoinitiators include Darocur 1173and Darocur 2959 (Ciba Specialty Chemicals). These and otherphotoinitators which may be used are disclosed in Volume III,Photoinitiators for Free Radical Cationic & Anionic Photopolymerization,2^(nd) Edition by J. V. Crivello & K. Dietliker; edited by G. Bradley;John Wiley and Sons; New York; 1998. The initiator is used in thereaction mixture in effective amounts to initiate photopolymerization ofthe reaction mixture, e.g., from about 0.1 to about 2 parts by weightper 100 parts of reactive monomer. Polymerization of the reactionmixture can be initiated using the appropriate choice of heat or visibleor ultraviolet light or other means depending on the polymerizationinitiator used. Alternatively, initiation can be conducted without aphotoinitiator using, for example, e-beam. However, when aphotoinitiator is used, the preferred initiators are bisacylphosphineoxides, such as bis(2,4,6-trimethylbenzoyl)-phenyl phosphine oxide(Irgacure 819®) or a combination of 1-hydroxycyclohexyl phenyl ketoneand bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide(DMBAPO), and in another embodiment the method of polymerizationinitiation is via visible light activation. A preferred initiator isbis(2,4,6-trimethylbenzoyl)-phenyl phosphine oxide (Irgacure 819®).

These reactive mixtures may be reacted “neat” or in the presence of adiluent. Suitable diluents and reaction conditions are known in the art.

In the examples the following test methods were used.

Advancing and receding contact angles were measured on a digital balance(WHITE Electrical Instruments) together with a moving stage (EalingOptical Co) which enabled the effective force during immersion andemersion to be obtained. The contact lens samples were cut into stripsof 3.3 mm wide. A maximum of 3 strips can be cut off one contact lens.Then a load is hooked at one extremity of the strip and crocodile clipclamps the other extremity (weight+hook=88.9±0.5 mg). This allowed thesample to remain straight during the analysis and prevent the lens fromfloating in the probe solution or curling. The advancing and recedingcontact angles were determined by reading the force at the point ofimmersion and emersion of the sample and were calculated using Young'sequation:

${\cos \; \theta_{a\text{/}r}} = \frac{F}{\gamma \; P}$

where: F=measured force (mN)

-   -   θ_(a/r)=advancing/receding contact angle (°)    -   γ=surface tension of probe solution (mN/m)    -   P=perimeter of test strip (m)

The hysteresis was calculated by subtracting the receding contact anglefrom the advancing contact angle.

The sessile drop contact angles reported in Examples 24-27 were measuredusing an automated Digidrop Contact Angle meter and technique (GBXScientific Instruments, Romans, France)

The equilibrium water contents were measured in phosphate bufferedsaline at 20° C. using the technique described in Synthetic Hydrogels 1,Copolymers of Hydroxyalkyl Acrylates and Methacrylates: Water BindingStudies, P H Corkhill, A M Jolly, C O Ng & B J Tighe, Polymer 1987, 28,1758-1766.

It will be appreciated that all of the tests specified herein have acertain amount of inherent test error. Accordingly, results reportedherein are not to be taken as absolute numbers, but numerical rangesbased upon the precision of the particular test.

In order to illustrate the invention the following examples areincluded. These examples do not limit the invention. They are meant onlyto suggest a method of practicing the invention. Those knowledgeable incontact lenses as well as other specialties may find other methods ofpracticing the invention. However, those methods are deemed to be withinthe scope of this invention.

In the examples, the following abbreviations are used:

AA=acrylic acid ACMO=acryloylmorpholine Am=acrylamide AMO=morpholinoacrylamide CAN=ammonium cerium (IV) nitrate DAT=diallyl tartramideDMA=N,N-dimethylacrylamide DMAEMA=N,N-dimethylaminoethyl methacrylateHEA=2-hydroxyethyl acrylamide HPA=2-hydroxy propylacrylateNaAMPS=sodium-2-(acrylamido)-2-methylpropane sulphonate NaVS=sodiumvinylsulfonate NIPA=N-isopropyl acrylamide NIPAm=N-isopropylacrylamideNVA=N-vinylacetamide NVMA=N-methyl-N-vinylacetamide NVP=N-vinylpyrrolidone PBS=phosphate buffered saline solution SPA=3-sulphopropylacrylate potassium salt THFA=tetrahydrofurfuryl methacrylateTRIS=N-(tris(hydroxymethyl)methyl)acrylamide EXAMPLES Examples 1-23

Grafting solutions were formed by mixing methylene bisacrylamide withwater to 0.5 weight %. The reactive anionic monomer listed in Table 1,below, and CAN, were added in the amounts listed in Table 1. Threedifferent lenses Lenefilcon A, lenses made according to Example 2 ofUS-2005-0070661 lenses; Dailies (Nelfilcon A, a PVA based contact lenscommercially available from CibaVision) and SeeQuence (Polymacon, apolyHEMA based contact lens commercially Bausch and Lomb) were contactedwith a grafting solution for the time and at the temperature listed inTable 1 and out-gassed with nitrogen. Each of the grafting solutionmixtures (Examples 5, 8, 10, 15 and 20), were a 50:50 molar mixture ofthe listed monomers. The lenses were removed from the grafting solutionand placed in distilled water for 3-5 days. The dynamic contact anglewas measured and is reported in Table 1, below. The dynamic contactangle for control lenses which were not contacted with the graftingsolution were also measured and are reported in Table 1, below.

TABLE 1 Reactive Anionic Rxn Adv. Rec. Monomer Temp. Time CA CAHysteresis Ex # (0.045 mol) (° C.) (hr) % CAN (°) (°) (°) Nelfilconlenses CE1 ex packing — — — 44 15 29 CE2 Saline washed* 66 34 32 1 SPA40 1 0.05 46 44 2 2 1 0.10 52 45 7 3 2 0.05 41 37 4 4 2 0.10 40 38 2 5SPA/TRIS 40 1 0.05 65 33 32 6 NaAMPS 40 1 0.05 44 37 7 7 1 0.10 52 33 198 NaAMPS/TRIS 40 1 0.05 49 26 23 9 TRIS 40 1 0.05 40 38 2 10 NaAMPS/SPA40 1 0.05 43 39 4 Lenefilcon lenses CE3 — — — — 54 35 19 11 SPA 40 10.05 46 40 6 12 1 0.10 57 36 21 13 2 0.05 46 35 11 14 2 0.10 58 38 20 15SPA/TRIS 40 1 0.05 68 34 34 16 NaAMPS 40 1 0.05 53 21 32 17 1 0.10 50 4010 18 50 2 0.10 18 13 5 19 60 2 0.10 42 36 6 20 NaAMPS/TRIS 40 1 0.05 8221 61 21 TRIS 40 1 0.05 62 36 36 Polymacon lenses CE4 — — — — 107 41 6622 SPA 40 1 0.05 86 41 45 23 NaAMPS 40 1 0.05 102 40 62

The lenses from Examples 1, 2, 6, 7, 12, 16, 17, 22 and 23 were testedfor the presence of sulfur as an indication of physical proof ofgrafting.

For each of the grafted lenses, sulfur was detected in the lenses ofExamples 1, 2, 6, 7, 12, 16 and 17. Sulfur was not detected on the lensof Examples 22 and 23 (SeeQuence/SPA), which may have been a peculiarityof the sample or a sign of irregular grafting. On the majority of thespectra, cerium (the initiator) was also noticeable. Sulfur was notpresent on any of the non-grafted control lenses.

It is believed that the chemical nature of the (polyvinyl alcohol-based)nelfilcon lens, which has a higher number of surface hydroxyl groups,provides more reactive sites for the grafting polymerization, whichaccounts at least in part for the significantly improved hysteresisdisplayed in Examples 1, 3, 4, 9 and 10. Graft polymerization of bothSPA and NaAMPS showed dramatically lower advancing contact angles andhystersis values. The appropriate control for comparison is ComparativeExample 2 (nelfilcon lens that was washed with saline for a similarperiod to that used in the grafting process). As shown from comparingCE1 and CE2, the washing step reduces the effect of leachable polyvinylalcohol on the hysteresis.

On the lenefilcon lenses, modification with both SPA and NaAMPS providedlenses with improved hysteresis (Examples 12, 13 and 17-19). When NaAMPSwas used as the volume excluding polymer better hysteresis was obtainedwhere reaction conditions were more vigorous (i.e. at higher reactiontemperatures of 50° C. or 60° C., longer reaction time (2 hr) and 0.10%initiator). For SPA, better hysteresis was achieved at lower SPAconcentrations.

Examples 24-27 and Comparative Examples 5-7

Ungrafted nelfilcon lenses from Comparative Example 2 and lenses ofExamples 3, 6 and 10 were placed into a 5 cm×5 cm glass cell and takenthrough identical humidity cycles, using an automated dynamic vapoursorption analyser (DVS). A schematic of this system is shown in FIG. 1.At the heart of the DVS system was an ultra-sensitive microbalance, 1,(Micrbalance Cahn D-200) capable of measuring changes in sample mass toless than 1 part in 10 million. The microbalance was housed in aprecisely controlled constant temperature incubator, 2, which ensuredvery high baseline stability as well as accurate control of the relativehumidity. Dry gas flow was controlled via mass flow controller 3 andsaturated vapour gas flows were controlled using mass flow controller 5,and vapour humidifier, 5. Humidity and temperature probes, 6, weresituated just below the sample and reference holders, 7 and 8,respectively, to give independent verification of system performance.The DVS was fully automated under control from a dedicatedmicrocomputer, not shown.

The conditions in the chamber were controlled as follows, temperaturewas maintained at 25° C. and humidity was controlled in a cycle of 40minutes at 98% relative humidity, followed by 2 minutes at 40% relativehumidity for 100 minutes.

After the full humidity cycle, the glass cells containing the lenseswere removed from the DVS cabinet and placed on the stage of animage-capture sessile drop contact angle apparatus (Digidrop ContactAngle Meter, GBX Scientific Instruments, Romans, France) located next tothe DVS cabinet and the change in contact angle was monitored. Theresults are shown in FIG. 2. As shown in FIG. 2, the unmodified lensesshowed a marked and progressive fall in contact angle as the surfacerehydrated whereas the grafted lenses of the present invention retaineda higher degree of hydration showed a much lower initial contact angleand little further change.

FIG. 2 shows that the lenses coated with ionic SPA and AMPS monomersshowed a greater affinity for water than do the untreated hydrogels. Thegrafted layer did not prevent dehydration of the lens, but it appears,maintained a higher degree of hydration and rehydrated preferentially.

Comparative Examples 8-11

The dehydration/rehydration dynamics of commercially available untreatedlenses (ACUVUE ONE DAY® brand contact lenses (commercially availablefrom Vistakon), DAILIES® brand contact lenses (commercially availablefrom CibaVision) and BIOCOMPATIBLE PROCLEAR® brand contact lenses), andhuman cornea were measured using the automated dynamic vapour sorptionanalyser (DVS) described in Examples 24-27, above. For each lensmeasured, the lens was placed in the sample holder, excess moisture wasremoved, and the relative mass loss of sample was measured at regularintervals throughout the humidity cycle. FIG. 3 shows the results fromthe analysis of three commercially available lenses. A sample of healthyhuman cornea was tested using the same procedure.

Examples 28-29

Etafilcon lenses (ACUVUE brand contact lenses, commercially availablefrom Vistakon) were removed from their packaging and rinsed withdistilled deionized water to remove saline. A coating solution was madehaving the components in the amounts shown in Table 2, below.

TABLE 2 Component Ex 28 Ex 29 Water (HPLC grade) 100 g  100 g SPA 10.44gm 0 NaAMPS 0 7.90 g PEG-acrylate 0 1.50 g CAN 0.15 0.15 Kpersulfate 0.50 MbA 0.13 0.13

The monomer(s) (anionic monomer and comonomer if used) were dissolved in50 gm of water, and nitrogen was bubbled through the solution for 10minutes. The CAN, potassium persulfate and MbA were dissolved in theother 50 gm of water. The lenses to be coated were immersed in the CANsolution, and the monomer solution was added to the CAN solution to formthe coating solution. Nitrogen was bubbled through the coating solution.The mixture was kept at 50° C., and a constant stream of nitrogen wasbubbled through the coating solution. After 4 hours the lenses wereremoved from the coating solution and then washed with distilled waterfor 20 minutes with gentle stirring. The wash solution was replaced withfresh distilled water and the wash step was repeated. The coated lenseswere placed in small vials containing saline solution (pH 7.4), sealedand sterilized at about 120° C. for about 20 minutes.

The hysteresis for the coated and uncoated lenses were measured. Thehysteresis for the SPA coated lenses was 3, compared to the hysteresisof 26 for the uncoated etafilcon lenses.

Examples 30-31

The lenses made in Examples 28-29 above were clinically evaluatedagainst untreated ACUVUE® ONE DAY brand contact lenses (etafilcon A).The clinical evaluation was a single masked (patient), randomized, studywith twenty patients completing the study.

The enrolled patients met the following criteria: aged 18 years orgreat, habitual daily soft contact lens wearers, with a best visualacuity of at least 6/9, symptomatic score >0.19 on CLDEQ (Nichols etal., 2002) and willing to adhere to the instructions set in the clinicalprotocol. The subjects were non-astigmatic (<1 DC) and free of ocularallergies, disease, active ocular infection, significant (Efron grade 3or greater) ocular tissue anomaly and not currently using any ocularmedication or systemic medication with ocular implications.

The patients wore the three lens types in a random order for 3 days,with assessment made on the afternoon of the third day. A minimum twoday period was allowed before the next lens type was evaluated.

Bulbar hyperaemia, palpebral roughness and corneal staining were gradedusing the CCLRU grading scale to 0.1 scale unit resolution. Nomicrocysts, straie, folds or infiltrates were observed during the trial.

The patients rated the lenses on a continuous visual analogue scale forthe following parameters: comfort, dryness, burning/stinging, visualclarity and photophobia. The ratings were made upon insertion (first 30minutes of wear), daytime (rest of the day up to 6 pm) and evening (from6 pm to contact lens removal) in a log book. Tables 3-5 shows the studyresults. Patients also recorded the number of hours the lenses wereworn. The average reported wear time for the lenses was as follows:Example 30 (SPA-coated lenses of Example 28) 11.05±2.81 hours, Example31 (AMPS-coated lenses of Example 29) for 12.01±2.45 hours and controllenses of Comparative Example 12 (uncoated etafilcon lenses) for10.90±2.79 hours per day.

TABLE 3 Subjective Ratings upon insertion Comfort Dryness Vision Ex. # MSD M SD M SD 30 78 22 83 17 77 26 31 88 15 86 14 88 16 Uncoated 75 23 7819 81 21

TABLE 4 Daytime subjective ratings Comfort Dryness Vision Ex. # M SD MSD M SD 30 71 27 73 25 70 31 31 80 20 74 27 94 98 Uncoated 66 29 64 2969 31

TABLE 5 Evening subjective ratings Comfort Dryness Vision Ex # M SD M SDM SD 30 59 30 58 31 65 33 31 76 27 72 29 80 21 Uncoated 58 32 54 32 6731The lenses of the present invention displayed comfort, dryness andvision which were at least as good, and in the case of Example 31,better than the uncoated control. All lenses displayed acceptablemovement and low staining.

Example 32

8 g (5.38% wt) of 2-hydroxyethyl acrylamide (in the form of a 45%solution in water), 40.0 g (49.80% wt) of sodium 2-acrylamido 2,2methylpropane sulphonate, (in the form of a 50% solution in water) and16.01 g (44.82% wt) of N-vinyl pyrrolidone together with 0.8 g (2% wt)of potassium persulphate (K₂S₂O₈) initiator were dissolved in a mixtureof 80 mls of acetonitrile and 120 mls of water. The mixture wasintroduced into a three-necked reaction flask equipped with stirrer,water condenser and nitrogen sparge and heated by an electric isomantle.The reaction mixture was heated to a temperature of 70° C. for a periodof 60 minutes. The reaction mixture was precipitated into an excessvolume of acetone, filtered and dried in a vacuum oven at 60° C. givinga 67% yield (26.5 g).

Recovered polymer was dissolved in PBS to form a 0.01 wt % solution ofpolymer. The polymer dissolved readily with gentle agitation on anorbital shaker. 100 ml of the 0.1% polymer solution was added to a 200ml autoclavable polypropylene plastic screwtop container. 1DAY ACUVUEbrand contact lenses, commercially available from Johnson & JohnsonVision Care, Inc. were placed into Histosette biopsy cassettes. ThreeHisosette cassesttes were placed into a 200 ml plastic screwtopcontainer, and the container top was screwed on. The container wasplaced into an autoclave. The container and lenses were autoclaved inthe 0.1% polymer solution for 30 minutes at 120° C. The containers wereremoved from the autoclave and the polymer solution replaced by PBS. Thelenses in the Histocassetes were washed/stored in PBS for at least twodays before performing the COF analysis, with at least two changes ofPBS. Tweezers were used to handle and transfer the lenses. Lenses werefound to have maintained their original dimensions following thisprocess.

The coefficient of friction of the_lenses was measured as follows. Ahigh sensitivity tribometer (CSM Nano Scratch Tester, CSM Instruments,Peseux, Switzerland) mounted on an air table was used for themeasurement of coefficient of friction. The test lens was placed on aconvex support and the coefficient of friction measured as the lensslides at a sliding speed of 5 mm/minute under a load of 3 mN/m a chosensubstrate (Melinex® (polyethylene terephthalate) film (DuPont) in thepresence of a lubricating solution (Hypotears® artificial tear solution(Novartis Ophthalmics).

For each sample ten repeat runs of 20 mm distance was measured. At leasttwo lenses were run under these conditions and the data from the lenseswere averaged. The COF for the lenses of this Example 32 were0.161±0.013.

Comparative Example 8

Example 32 was repeated, except that PBS without any polymer was used asthe sterilization solution. The COF of the untreated lenses was measuredto be 0.47.

Examples 33-42

Example 32 was repeated using the components and conditions listed inTable 6-8 below. COF was measured for Examples 36, 37, 39, 40, 42, 44,45, 47, 49, 50 and 52, and is shown in Table 9, below.

TABLE 9 Ex # COF 36 0.224 37 0.204 39 0.224 40 0.175 42 0.295 44 0.26245 0.229 47 0.143 49 0.291 50 0.162 52 0.200

Thus, compared to the control which had a COF of 0.47, the lenses of thepresent invention displayed significant improved COF.

TABLE 6 Rxn PPT Vol time Evd. prod % Ex# HEA NaAMPS NVMA ACMO NVP DMAHEAc K₂S₂O₈ (ml) (min) polym PPT (g) conv 33 9.06 40.08 8 8.02 0 0 0 0.4200 150 PA yes 17.35 43.2 34 0 40.03 8.03 8.07 0 0 4.11 0.4 200 150 PAYes NM NM 35 0 40.6 8.09 8.08 0 0 4.0 0.4 200 120 PA Yes NM NM 36 039.98 8.01 8.01 0 0 4.12 0.4 200 90 VR* Yes 10.38 54¹  37 9.53 40.018.03 8.03 0 0 0 0.4 200 150 VR yes 14.02 34.8 38 2 10 2 0 2 0 0 0.2 100NT NM NM 39 4.5 20 12 12 0 0 0 0.8 200 60 VR*, Yes 20.07 55.4 PA 40 4.560 4 4 0 0 0 0.8 200 25 VR, Yes 13.36  66.8¹ PA 41 2.4 20 0 0 0 9 0 0.4200 90 VR, yes 14.82 73.8 PA 42 0.5 10 2.25 0 0 2.25 0 0.2 100 10 PA yes3.07 31.6 PA = precipitate in acetone VS = viscosity rise *greasy linesobserved ¹only half of solution precipitated NM = not measured NT = nottried

TABLE 7 Rxn PPT DMA Vol time Evd. prod % Ex# HEA NaAMPS NVMA Am NIPAmTHFA EMA NVA K₂S₂O₈ (ml) (min) polym PPT (g) conv 43 2 10 2 2 0 0 0 00.2 100 90 PA yes NM NM 44 8 40 8 0 4 0 0 0 0.8 200 90 Pink*, PA Yes yes10.43 45 6.12 41.19 8.01 0 0 10.18 0 0 0.2 200 Color, Yes 10.35  49.81¹PA 46 1.59 10.52 2.15 0 0 0 2.91 0 0.2 100 90 PA Yes NM NM 47 8 40 8 0 00 0 8 0.8 200 90 PA yes NM NM 48 8 15 15.5 0 0 0 0 15.5 0.8 200 90 PAYes NM NM PA = precipitate in acetone VS = viscosity rise *greasy linesobserved ¹only half of solution precipitated NM = not measured

TABLE 8 Rxn PPT Vol time Evd. prod % Ex# HEA SPA NVMA ACMO NaVS K₂S₂O₈(ml) (min) polym PPT (g) conv 49 10.07 20.58 8.55 8.37 0 0.8 200 90 *PAyes 10.17  48.38¹ 50 9.68 0 8.05 8.08 66.86 0.8 200 90 Color, Yes NM NMPA 51 8 20 8 0 0 0.8 100 90 PA Yes NM 39.6 52 8 0 8 0 67 0.8 100 90 PAYes NM 39.7 PA = precipitate in acetone *greasy lines observed ¹onlyhalf of solution precipitated NM = not measured

1. A composition comprising a polymer comprising at least one volumeexcluding polymer.
 2. The composition of claim 1 wherein said volumeexcluding polymer is formed from a reaction mixture comprising optionalcomonomers and at least one reactive anionic monomer comprising at leastone hydratable polyanion group.
 3. The composition of claim 1 whereinsaid hydratable polyanion group is distributed substantially uniformlythroughout said volume excluding polymer.
 4. The composition of claim 3wherein said reactive anionic monomers are of the formula:R-L-A wherein R is a reactive group, L is a linking group and A is ahydratable polyanion group.
 5. The composition of claim 4 wherein R is afree radical reactive group selected from the group consisting of(meth)acrylates, styryls, vinyls, vinyl ethers,C₁₋₆alkyl(meth)acrylates, (meth)acrylamides, C₁₋₆alkyl(meth)acrylamides,N-vinyllactams, N-vinylamides, C₂₋₁₂alkenyls, C₂₋₁₂alkenylphenyls,C₂₋₁₂alkenylnaphthyls, C₂₋₆alkenylphenylC₁₋₆alkyls, O-vinylcarbamatesand O-vinylcarbonates.
 6. The composition of claim 4 wherein R is a freeradical reactive group selected from the group consisting of(meth)acrylate, acryloxy, (meth)acrylamide, and mixtures thereof.
 7. Thecomposition of claim 4 wherein R is selected from the group consistingof vinyl ethers or epoxide groups, alcohols, esters, carboxylic acids,isocyanates, anhydrides, groups capable of halide displacement, cyclicderivatives of hydroxyl and amino carboxycylic acids, cyclic ethers,cyclic esters, cyclic amides and combinations thereof.
 8. Thecomposition of claim 4 wherein L is selected from the group consistingof substituted and unsubstituted alkylene having 1-12 carbon atoms,which may be straight or branched, polyethers, oxazolines, substitutedand unsubstituted heterocyclic groups and combinations thereof.
 9. Thecomposition of claim 4 wherein A is selected from the group consistingof phosphates, phosphonates, borates, sulfates, sulfonates andcombinations thereof.
 10. The composition of claim 4 wherein A comprisesat least one sulfonate group.
 11. The composition of claim 2 whereinsaid reactive anionic monomers have the formulaH₂C═C(R₂)—CO₂—(CH₂)_(n)-A wherein R₂ is selected from —H, —CH₃,—CH₂CO₂—(CH₂)_(n)-A, where n is an integer between 2 and 8 and A is ahydratable polyanion group.
 12. The composition of claim 11 wherein A isselected from the group consisting of phosphates, phosphonates, borates,sulfates, sulfonates and combinations thereof.
 13. The composition ofclaim 11 wherein A comprises at least one sulfonate group.
 14. Thecomposition of claim 1 wherein said volume excluding polymer is anoligomer having a molecular weight of at least about
 500. 15. Thecomposition of claim 1 comprising at least two volume excludingpolymers, a first volume excluding polymer having a molecular weight ofless than about 10,000 and a second volume excluding polymer havingmolecular weight of greater than about 100,000.
 16. The composition ofclaim 3 further comprising at least one physiologically compatiblecation anionically bound to said polyanion groups.
 17. The compositionof claim 16 wherein said cation is selected from the group consisting ofLi+, Na⁺, K⁺, NH₄ ⁺, Mg⁺, Zn⁺, Ag+, and combinations thereof.
 18. Thecomposition of claim 16 wherein said cation is selected from the groupconsisting of Na⁺, K⁺ and mixtures thereof.
 19. The composition of claim2 wherein said reactive anionic monomers is selected from the groupconsisting of sodium-2-(acrylamido)-2-methylpropane sulphonate,3-sulphopropyl (meth)acrylate potassium salt, 3-sulphopropyl(meth)acrylate sodium salt, 3-sulphopropyl (meth)acrylate calcium salt,di-potassium salt of bis-3-sulfopropylester (meth)acrylate, di-calciumsalt of bis-3-sulfopropylester (meth)acrylate, di-sodium salt ofbis-3-sulfopropylester (meth)acrylate, styrene sulfonate and mixturesthereof.
 20. The composition of claim 2 wherein said volume excludingpolymers comprise between about 20 and about 80 wt % repeating unitsderived from reactive anionic monomers.
 21. The composition of claim 2wherein said volume excluding polymers are formed from a reactionmixture comprising between about 20 to about 80 mol % said reactiveanionic monomers and comonomers comprising about 2 and about 80 mol %amide-containing comonomers, from 0 to about 40 mol % carboxylicacid-containing comonomers and from 0 to about 40 mol %hydroxyl-containing comonomers.
 22. The composition of claim 2 whereinsaid at least one comonomer comprises at least one hydrophilicvinyl-containing monomer selected from the group consisting of N-vinylamides, N-vinyl lactams, N-vinyl acetamide, N-vinyl-N-methyl acetamide,N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide,2,2-di methoxy, 1-hydroxy acrylamide, hydroxymethyl diacetoneacrylamide, N-acryloyl morpholine, hydroxyl methylacrylamide andcombinations thereof.
 23. The composition of claim 30 wherein said atleast one comonomer comprises at least one hydrophilic monomer selectedfrom the group consisting of N,N-dimethylacrylamide, 2-hydroxyethylmethacrylate, glycerol methacrylate, 2-hydroxyethyl methacrylamide,N-vinyl pyrrolidone, N-vinyl-N-methyl acrylamide,N-methyl-N-vinylacetamide, polyethyleneglycol monomethacrylate,methacrylic acid, acrylic acid, N-(tris(hydroxymethyl)methyl)acrylamide,itaconic acid and combinations thereof.
 24. The composition of claim 1wherein said volume excluding polymer has a structure selected from thegroup consisting of brush structure, branched structure, loopedstructure, or a combination thereof.
 25. The composition of claim 1wherein said volume excluding polymer forms an interpenetrating networkwith at least a portion of said polymer.
 26. A device formed from ahydrated polymer and at least one volume excluding polymer in aconcentration sufficient to act as an osmotic driver.
 27. The device ofclaim 26 wherein said device comprises a first surface and a secondsurface and of said volume excluding polymer concentration varies fromsaid first surface to said second surface.
 28. The device of claim 26wherein said volume excluding polymer is present on only one surface ofsaid device.
 29. The device of claim 26 wherein said device is a contactlens.
 30. The contact lens of claim 29 where said first surface is afront contact lens surface disposed during use in contact with an eyelidof a contact lens wearer and said second surface is a back surfacedisposed against the contact lens wearer's eye.
 31. The contact lens ofclaim 30 wherein said front contact lens surface is coated with saidvolume excluding polymer.
 32. The contact lens of claim 30 wherein theconcentration of said volume excluding polymer is greater at the frontcontact lens surface.
 33. The contact lens of claim 30 wherein saidvolume excluding polymer is located within 5 um of said front contactlens surface.
 34. The contact lens of claim 30 wherein said contact lensis a contact lens formed from a hydrogel having a water content of atleast about 5 weight %.
 35. The contact lens of claim 34 wherein saidhydrogel is a silicone hydrogel.
 36. The device of claim 26 wherein saiddevice is selected from the group consisting of wound healing materials,and therapeutic ophthalmic dressings, and intervertabrate diskreplacements.
 37. A method comprising incorporating at least one volumeexcluding polymer in or on at least one substrate.
 38. The method ofclaim 37 wherein said incorporating is achieved via a method selectedfrom the group consisting of covalent or ionic attachment of said volumeexcluding polymer to at least a portion of at least one surface of thesubstrate, coating said volume excluding polymer onto at least onesurface of said substrate, imbibing said volume excluding polymer intoall or part of said substrate; polymerizing said volume excludingpolymer with the reactive mixture from which the substrate is made,reacting a reactive anion group in the presence of at least a part ofsaid substrate and combinations thereof.
 39. The method of claim 37wherein said volume excluding polymer is present on at least one surfaceof said substrate.
 40. The method of claim 37 wherein said volumeexcluding polymer is formed from reaction anionic monomers comprising atleast one hydratable polyanion group selected from the group consistingof phosphates, phosphonates, borates, sulfates, sulfonates andcombinations thereof.
 41. The method of claim 40 wherein said hydratablepolyanion group comprises at least one sulfonate group.